Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinase 9 (MMP-9) is a Zn(2+)-dependent endopeptidase that degrades some of the components of basement membranes and extracellular matrix and thus participates in leukocyte infiltration during inflammation. In a model of zymosan peritonitis, neutrophil infiltration in MMP-deficient (MMP-9(-/-)) mice was significantly weaker at the time of their maximal influx in wild-type mice (6h). However, during the late stages of peritonitis (24h) an extended accumulation of neutrophils was observed in MMP-9(-/-)versus the wild-type mice. Recently, we reported that the ratio of apoptosis of inflammatory leukocytes is impaired in MMP-9(-/-) mice during late peritonitis and the process depends on COX-1-driven PGE(2). Here we scrutinized the alterations in apoptotic mechanisms by comparisons between MMP-9(-/-) and the wild-type mice. Altered apoptosis occurred only during late (24h) peritonitis and concerned only neutrophils, and not macrophages, mast cells or lymphocytes. Furthermore, expression and activity of caspases was altered in MMP-9(-/-) animals, delayed for caspase-8 and -9, and decreased in the case of caspase-3. Also the expression of Bax/Bcl-2 proteins was changed in MMP-9(-/-) mice. These changes, and in particular the impaired neutrophil apoptosis and weaker caspase-3 activity, were restored by the selective COX-1 inhibition. We conclude that in mice lacking MMP-9 the enhanced COX-1-PGE(2) decreases caspase-3 expression and activity leading to impaired apoptosis of inflammatory neutrophils resulting in abnormal accumulation of the cells at the inflammatory focus. The data also reinforce the notion that MMP-9 is a key enzyme in neutrophil biology.
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PMID:Altered apoptosis of inflammatory neutrophils in MMP-9-deficient mice is due to lower expression and activity of caspase-3. 1968 97

Matrix metalloproteinase 9 is a zinc-dependent extracellular matrix remodeling endopeptidase directly involved in the local invasion mechanisms and in metastasis. The current review aims to evaluate the expression of MMP-9 and its prognostic value in the most common epithelial and lymphatic neoplasia of the pelvic-abdominal region. We included 19 studies published between January 1st, 1995 and July 31st 2015, involving a total of 1523 patients. The analysis indicate that MMP-9 is valid marker of poor survival in epithelial and lymphatic neoplasia.
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PMID:The Role of Matrix Metalloproteinase-9 (MMP-9) as a Prognostic Factor in Epithelial and Lymphatic Neoplasia. 2671 23

Matrix metalloproteinase 9 (MMP-9) is an extracellularly operating zinc-dependent endopeptidase that is commonly expressed in the brain, other tissues. It is synthesized in a latent zymogen form known as pro-MMP-9 that is subsequently converted to the active MMP-9 enzyme following cleavage of the pro-domain. Within the central nervous system, MMP-9 is localized and released from neurons, astrocytes and microglia where its expression levels are modulated by cytokines and growth factors during both normal and pathological conditions as well as by reactive oxygen species generated during oxidative stress. MMP-9 is involved in a number of key neurodevelopmental processes that are thought to be affected in schizophrenia, including maturation of the inhibitory neurons that contain the calcium-binding protein parvalbumin, developmental formation of the specialized extracellular matrix structure perineuronal net, synaptic pruning, and myelination. In this context, the present article provides a narrative synthesis of the existing evidence linking MMP-9 dysregulation to schizophrenia pathogenesis. We start by providing an overview of MMP-9 involvement in brain development and physiology. We then discuss the potential mechanisms through which MMP-9 dysregulation may affect neural circuitry maturation as well as how these anomalies may contribute to the disease process of schizophrenia. We conclude by articulating a comprehensive, cogent, and experimentally testable hypothesis linking MMP-9 to the developmental pathophysiologic cascade that triggers the onset and sustains the chronicity of the illness.
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PMID:A conceptualized model linking matrix metalloproteinase-9 to schizophrenia pathogenesis. 3200 Oct 79